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Engineering CAR T Cells Inside Solid Tumors
Researchers develop targeted lipoplex platform that generates CAR T and NK cells directly within tumors, improving survival in preclinical breast cancer models
Researchers developed R8L-NI@Lipo, a tumor-targeted lipoplex designed to generate CAR-expressing T cells and NK cells within solid tumors.
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The lipoplex delivers plasmid DNA encoding an NKG2D-based CAR and IL-15, with hypoxia-responsive elements designed to limit CAR expression to low-oxygen tumor environments.
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In mouse models, the targeted lipoplexes accumulated in tumors and penetrated beyond tumor blood vessels, while CAR expression was higher under hypoxic conditions.
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In the 4T1 model, treatment increased CD8+ T-cell infiltration 3.33-fold versus untreated controls, reduced mean tumor weight to about 9.2% of control, and produced complete regression in 2 of 6 mice.
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Median survival increased from 22.5 to 42.5 days in the 4T1 model and from 22.5 to 44.5 days in the EMT6 model; safety findings suggested reduced off-target effects with hypoxia-responsive regulation.
Patients with estrogen-receptor-positive (ER+) HER-2-negative advanced breast cancer experienced significantly improved progression-free survival (PFS) when treated with an oral combination regimen that included giredestrant, a novel, next-generation selective ER degrader and full antagonist (SERD), compared to a standard combination approach.
